RPI, UNC researchers make ‘critical advance in safety’

TROY >> Researchers at Rensselaer Polytechnic Institute, among others, have created a synthetic drug with the ability to save lives.

Researchers from RPI and University of North Carolina (UNC) created synthetic form of low molecular weight heparin, an anticoagulant commonly used around the world to prevent dangerous blood clots. The synthetically-produced drug is safer and can be used in more applications than the animal-derived alternative.

“This is a drug that millions of people rely upon, and it’s important to develop a safe, synthetic alternative to the current supply chain,” said Robert Linhardt, one of the inventors from RPI.

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Heparin has been used since the 1930s to prevent blood clots during and after procedures including kidney dialysis, heart bypass surgery, stent implantation, and knee and hip replacement. About 5 percent of patients receiving heparin experience some form of uncontrolled bleeding.

Researchers have worked for years to find the best process and exact structure to make the drug. Linhardt and his colleagues have been actively addressing this endeavor since 2008, after a contaminated natural form of the drug killed more than 80 Americans, causing hundreds to suffer adverse reactions. Heparin is typically extracted from pig intestines in China. “Since that time, we’ve been interested in preparing heparin from non animal sources,” he said.

A team led by Linhardt and Jian Liu, a professor in the UNC Eshelman School of Pharmacy, created the synthetic version of low molecular weight heparin.

The heparin research was funded by the National Institutes of Health. Liu and Linhardt’s co-authors include Lingyun Li, a Rensselaer research assistant professor, and Chao Chi, a Rensselaer post-doctoral fellow.

Among the new advantages, “The synthetic version that we’ve made is reversible, it can be used in renal patients, and it doesn’t come from animals, which is a critical advance in safety,” Linhardt said.

Because the new version does not come from animals, it is safer and more manageable. “We felt that the best way to approach this was to separate the food chain from the drug chain,” calling the combination a potential for disaster.

Another major improvement is the ability to easily reverse cases of heparin overdose. Linhardt and Liu engineered their drug’s molecular structure so that protamine can deactivate it, a process that was never before possible.

Specifically for patients with poor kidney function, the newly enhanced drug is a safe alternative. The original drug had a limited ability to be cleared through kidneys. Linhardt and Liu made additional changes, allowing their drug to bind to receptors that clear it through the liver, rather than the kidney, making it safe for renal patients.

The new version is an economically viable alternative to the existing imported supply.

Now, the inventors are hoping for a pharmaceutical company to push the new drug through U.S. Food and Drug Administration approval. The drug has been tested in rodents, but must be further evaluated in animals, then humans, before approval.

“Now the issue become the business model,” Linhardt said. “We’re hoping that we have commercial interest, and we’re looking forward to actually designing what will ultimately go to the people.” Worldwide sales of heparin are estimated at $4 billion annually.

Someday, the synthetic drug could be manufactured cost effectively within the country. Linhardt estimates it could be another 5 years before hospital patients can experience the benefits of his research.